Health Professionals
Patients & Families
Careers 
CRISPR-Based Genome-Editing Therapy for Hemoglobin Disorders
Investigating a personalized ex vivo genome-editing approach to reactivate protective fetal hemoglobin (HbF) in patients with transfusion-dependent β-thalassemia and sickle cell disease.
By utilizing precision CRISPR-Cas9 ribonucleoprotein systems to target the erythroid-specific enhancer of the BCL11A gene, our research aims to eliminate repressive signaling and harness the body’s natural developmental biology to produce healthy, functional red blood cells.
Understanding β-Thalassemia & Sickle Cell
β-Thalassemia is caused by genetic mutations in the HBB gene that impair the synthesis of adult hemoglobin beta-chains, resulting in severe anemia, ineffective erythropoiesis, and dependence on lifelong blood transfusions.
Sickle cell disease is caused by a specific point mutation in HBB creating abnormal hemoglobin S (HbS). Under hypoxia, HbS polymerizes, distorting red blood cells into rigid sickle shapes that obstruct microvessels, leading to acute vaso-occlusive pain crises, stroke risk, and progressive end-organ damage.
Why target the BCL11A Enhancer?
BCL11A is the master transcription factor that silences fetal hemoglobin (HbF) expression in early infancy during the physiological transition from gamma-globin to beta-globin production.
Rather than disrupting the entire BCL11A gene (which is required for normal B-cell development), our CRISPR strategy selectively edits the erythroid-specific enhancer. This lineage-restricted disruption derepresses gamma-globin specifically in erythroid precursors, driving high-level HbF synthesis without compromising other blood cell lineages.
How CRISPR-based stem cell therapy works
Genetically correcting the regulatory switch in autologous hematopoietic stem and progenitor cells (HSPCs).
Collecting stem cells
Following pharmacological mobilization, the patient’s own CD34+ hematopoietic stem cells are collected via apheresis and purified under cleanroom conditions.
CRISPR Editing
Purified stem cells undergo high-efficiency electroporation with Cas9 ribonucleoprotein (RNP) complexes, making precise cuts within the BCL11A erythroid enhancer.
Quality Evaluation
Edited cell pools are cryopreserved and subjected to NGS indel quantification, off-target cleavage verification, viability testing, and sterility certification.
Engraftment & HbF
Edited stem cells are infused intravenously. Upon homing to the bone marrow, they establish lifelong hematopoiesis, producing red blood cells with elevated fetal hemoglobin.
The 6-Step Clinical Treatment Pathway
General prospective process associated with autologous ex vivo genome-editing and stem cell transplantation.
Medical Evaluation
Comprehensive baseline assessment of transfusion frequency, baseline HbF, hepatic/cardiac iron burden (T2* MRI), and organ reserve.
Stem Cell Collection
Administration of mobilization agents (plerixafor / G-CSF) followed by leukapheresis to harvest sufficient CD34+ progenitor cells.
Genome Editing in Cleanrooms
Cellular editing, cold storage, and analytical batch release testing confirming targeted indel frequency and absence of chromosomal anomalies.
Marrow Conditioning
Myeloablative conditioning (busulfan) administered in specialized transplant units to clear bone marrow niches for incoming edited cells.
Stem Cell Re-infusion
Thawing and intravenous infusion of the edited autologous product with continuous vital sign monitoring and anaphylaxis precautions.
Engraftment & Follow-up
Inpatient supportive care until neutrophil/platelet engraftment, followed by serial evaluation of HbF levels, transfusion independence, and safety.
Biological Mechanism of HbF Reactivation
Harnessing natural developmental biology to bypass mutated adult beta-globin genes through genetic derepression of gamma-globin.
Biological Sequence
Genome Editing
Precision single-guide RNA designs targeting the core GATA1 motif within the BCL11A enhancer.
Stem Cell Biology
Preserving long-term self-renewing hematopoietic stem cell clones during ex vivo handling.
Personalized Cell Therapy
Autologous administration eliminating graft-versus-host disease (GvHD) and donor matching barriers.